Device

ABSTRACT

A drug delivery device for delivering to a patient a drug composition from a container which contains the drug composition where the container is adapted to be placed in a dispensing mode thereof on application of an actuating condition thereto is disclosed. The device includes a dispensing unit adapted to receive the container, the dispensing unit having an actuating mechanism operable to apply the actuating condition to the container and an outlet through which the drug composition is dispensable from the device, and a removable casing unit for the dispensing unit. The dispensing and casing units have securing features for releasably, fixedly securing the units together, and the dispensing unit is operable to apply the actuating condition to the container when fixedly secured to the casing unit and when independent from the casing unit.

RELATED APPLICATIONS

This International patent application claims priority from UK patentapplication No. 0226022.2 dated 7 Nov. 2002 and is related to theApplicant's concurrently filed International patent applications whichrespectively claim priority from UK patent application No. 0226021.4dated 7 Nov. 2002 (Applicant's Ref: P33143) and UK patent applicationNo. 0226020.6 dated 7 Nov. 2002 (Applicant's Ref: P33145). The entirecontent of each of these applications is hereby incorporated herein byreference.

FIELD OF THE INVENTION

The present invention relates to a drug delivery device for deliveringto a patient a drug composition from a container which contains the drugcomposition, the container adapted to be placed in a dispensing modethereof on application of an actuating condition thereto (hereinafter a“device of the type defined”).

BACKGROUND OF THE INVENTION

Before a device of the type defined can be legally marketed, it is firstnecessary for the device to be approved by the appropriate regulatoryauthority, e.g. the Food and Drug Administration (FDA) in the UnitedStates of America.

The present invention proposes to provide a device of the type definedwhich can shorten the lead time for it to get to market.

SUMMARY OF THE INVENTION

According to the present invention there is provided a device of thetype defined comprising:

-   -   a dispensing unit adapted to receive the container, the        dispensing unit having an actuating mechanism operable to apply        the actuating condition to the container and an outlet through        which the drug composition is dispensable from the device; and    -   a removable casing unit for the dispensing unit;    -   with:    -   the dispensing and casing units having securing features for        releasably, fixedly securing the units together; and    -   the dispensing unit being operable to apply the actuating        condition to the container when fixedly secured to the casing        unit and when independent from the casing unit.

Preferably, the casing unit is movable between a closed state in whichit is able to enclose the dispensing unit with the container receivedtherein, and an open state which enables the actuating mechanism of thedispensing unit to be operated to apply the actuating condition to thecontainer and for the resultant dispensed drug composition to bedischarged from the outlet.

The device may be hand-held, for instance the device may be adapted tobe held by the casing unit when assembled with the dispensing unit.Preferably, the dispensing unit is adapted to be hand-operated to applythe actuating condition to the container. For example, the device may beadapted so that, when the casing unit is held by a hand of a patient,the hand of the patient is also able to operate the actuating mechanismof the dispensing unit.

Preferably, the actuating condition is movement of a first part of thecontainer relative to a second part and the actuating mechanism of thedispensing unit is able to effect said relative movement. As an example,the actuating mechanism of the dispensing unit is adapted in use to holdthe second part of the container stationary and to allow the first partto move relative thereto.

The container may have a plurality of doses of the drug composition andbe fitted with a dose counter mechanism, and the dispensing unit has adose counter advancing mechanism adapted in use to advance the dosecounter mechanism when the actuating condition is applied by thedispensing unit to the container. Conveniently, the dose counteradvancing mechanism has a mechanical feature which engages the dosecounter mechanism to advance it on relative movement of the first partof the container to the second part thereof. The mechanical feature maybe a post and/or a part of a rack-and-pinion mechanism, the other partbeing in the dose counter mechanism.

Ideally, the outlet forms a part of a nozzle arrangement in thedispensing unit for directing the drug composition to the patient onapplication of the actuating condition to the container.

The second part of the container may present an outlet of the container.In use, the outlet of the container is preferably held stationary by thenozzle arrangement. Preferably, the second part is a valve which ismoved between a closed position and an open position on relativemovement with the first part. In an embodiment of the invention, such ashereinafter described, the container is an aerosol container with thefirst part a canister.

According to the invention there is further provided the device of theinvention in combination with the container and the drug compositiontherein. The drug composition may be for the treatment or prophylaxis ofa respiratory disease or disorder, e.g. rhinitis.

The device may be an inhalation device or an intranasal device.

According to the invention there is also provided a drug delivery systemcomprising the device of the invention and at least one furtherdispensing unit, the dispensing units being interchangeable with oneanother. So, refill containers could be supplied “ready-for-use” in areplacement dispensing unit.

The present invention also provides a drug delivery system comprisingthe device of the invention and at least one further casing unit ofdifferent appearance to the other casing unit, the casing units beinginterchangeable with one another. Thus, removing the dispensing unitfrom one of the casing units and placing it in the other casing unitgives the drug delivery device a new appearance. In other words, theaesthetics, but not the functionality, of the device can be customizedto certain patient groups, e.g. based on demographics, nationality etc.

The present invention yet further provides a method of manufacturing adrug delivery device for delivery of a drug formulated in a drugcontainer which is adapted to be placed in a dispensing mode onapplication of an actuating condition thereto, the method comprising thesteps of:

-   -   (a) providing a dispensing unit for receiving the container        which has an actuating mechanism for applying the actuating        condition thereto and an outlet through which the drug        formulation is dispensable from the dispenser on application of        the actuating condition thereto, and    -   (b) separately providing a casing unit adapted to fixedly hold        the dispensing unit such that the drug is dispensable from the        container by the dispensing unit when held by the casing unit.

The invention additionally provides a drug delivery device formed by themethod of the invention.

Further preferred features of the invention are set forth in the claimsappended hereto.

A non-limiting exemplary embodiment of the invention will now bedescribed with reference to the accompanying FIGURES of drawings.

BRIEF DESCRIPTION OF THE DRAWINGS OF THE EXEMPLARY EMBODIMENT

FIG. 1 is a schematic view of a patient using an intranasal device inaccordance with the invention.

FIG. 2 is a side view of the intranasal device showing an outer casingpart thereof comprising cover and container members and a hingetherebetween, the outer casing part in a closed state to protect innerparts of the device.

FIG. 3 is a side view of the intranasal device with the outer casingpart hinged to an open state to allow access to the inner parts.

FIG. 4A is a side view of the intranasal device in its open state withthe cover member pivoted behind the container member

FIG. 4B corresponds to FIG. 4A, but with the container and cover membersnested.

FIG. 5 is a rear view of the device with the outer casing part in itsclosed state.

FIG. 6 is an exploded perspective view of the intranasal device with theouter casing part in its nested state.

FIG. 7 is a schematic, partial sectional side view of an inner actuatingpart of the intranasal device mounted in the outer casing part.

FIG. 8 is a enlarged fragmentary view of an alternative hingeconstruction for the outer casing part.

FIG. 9 is a cross-sectional side view of the alternative hingeconstruction along line IX-IX in FIG. 8.

FIG. 10A is a perspective view of a canister unit of the intranasaldevice comprising a canister and a dose counter head mounted on thecanister.

FIG. 10B is a plan view of the dose counter head.

FIG. 10C is a side view of the dose counter head.

FIG. 10D is a rear view of the dose counter head.

FIG. 11 is schematic side view, partly in section, of the inneractuating part of the intranasal device.

FIG. 12 is an opposite side view of the inner actuating part with thecanister unit shown mounted therein in ghost.

FIG. 13 is a plan view of the inner actuating part.

FIG. 14 is a rear view of the inner actuating part with the canisterunit mounted therein.

FIG. 15A is a schematic side view, partly in cross section, of thecanister unit mounted in the inner actuating part in an inoperativeposition.

FIG. 15B corresponds to FIG. 15A, but with the canister unit in anoperative position relative to the inner actuating part.

DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENT

In the FIGURES of drawings there is shown a drug delivery device 1 inaccordance with the present invention, the device 1 in this particularnon-limiting embodiment being an intranasal drug delivery device, asshown graphically in FIG. 1.

As best shown in FIG. 6, the intranasal drug delivery device 1 comprisesas component parts the following:

an outer casing part 3;

-   -   a one-piece inner actuating part 5 which is releasably securable        in the outer casing part 3; and    -   a canister unit 7 releasably securable in the inner actuating        part 5.        Outer Casing Part

Referring to FIGS. 2 to 7, the outer casing part 3 of the intranasaldevice 1 is formed from two shell-like members, namely a containermember 9 and a cover member 11, which are connected to one anotherthrough a hinge 13. The container and cover members 9, 11 eachrespectively present a cavity 17 a; 17 b having a mouth bound by a lipsurface 2 a; 2 b (FIG. 6).

Both the container member 9 and the cover member 11 are formed from aplastics material by injection moulding, although other types ofmoulding processes can, of course, be used. The container and covermembers 9, 11 are preferably both formed from polypropylene with thecontainer member 11 being opaque, but with the cover member 11 beingtransparent or semi-transparent. Other plastics material combinationsare possible, although it is preferable for the cover member 11 to betransparent/semi-transparent for reasons which will become apparenthereinafter.

As shown in FIG. 7, for example, the cover member 11 is integrallyformed with the hinge 13, colloquially known as a “living hinge”, andthe hinge 13 includes a knob 15.

Turning to FIGS. 6 and 7, on an inner surface 19 of the cavity 17 a ofthe shell-like container member 9 there is formed a pair of protrusionsor ribs 21 a, 21 b to co-operate with complementary surfaces of theinner actuating part 5 to form a snap-fit connection between the outercasing part 3 and the inner actuating part 5, as will also be discussedin more detail hereinafter. A first one of the ribs 21 a is disposedtowards an upper end 23 of the container member 9, whereas the other rib21 b is disposed towards a lower end 25 of the container member 9.

Also formed on the inner surface 19 of the cavity 17 a of the containermember 9 are longitudinally extending ribs 27 a, 27 b. The longitudinalribs 27 a, 27 b are disposed on opposing sides of the container member 9and act as anti-rotational retainers on the inner actuating part 5 inthe cavity 17 a.

At the upper end 23 of the container member 9 there is formed a bevel 29through which an aperture 31 extends from an outer surface 33 of thecontainer member 9 to the inner surface 19 of the cavity 17 a. From FIG.7 it will be seen that the aperture 31 is adapted to receive the knob 15on the hinge 13. Although the diameter of the knob 15 is greater thanthe diameter of the aperture 31, the knob 15 is able to be pushedthrough the aperture 31 for capture therein due to the container andcover members 9, 11 being sufficiently resiliently deformable due totheir shell-like nature and the materials used. Moreover, the knob 15 isable to be withdrawn from the aperture 31 upon application of asufficient pulling force thereto for separation of the container andcover members 9, 11.

As shown in FIGS. 2 to 5, the mounting of the knob 15 of the hinge 13 inthe aperture 31 of the container member 9 enables two degrees ofmovement of the cover member 11 on the container member 9 as follows:

-   -   (1) Hinging of the cover member 11 from a closed position shown        in FIGS. 2 and 5, in which the respective lip surfaces 2 a, 2 b        of the cavities 17 a, 17 b of the container and cover members 9,        11 abut one another at an interface 2 c to form an enclosed        internal space 8 (see FIG. 7), to an open position shown in FIG.        3, in which the cavity 17 a of the container member 9 is        accessible. As will be understood from FIGS. 6 and 7, the lip        surfaces 2 a, 2 b are each provided with detent elements 4, 6        which engage with one another in the closed position to provide        a releasable snap-fit fastening of the container and cover        members 9, 11 in the closed position.    -   (2) Rotary or pivotable movement of the cover member 11 about        the aperture 31 (pivot axis A-A) from a first angular position        corresponding to the open position shown in FIG. 3 to a second        angular position shown in FIG. 4A in which the cover member 11        is located behind the container member 9. The cover member 11 is        not able to be pivoted about the pivot axis A-A from its closed        position due to the interengagement of the lip surfaces 2 a, 2        b.

As shown in FIG. 4B, when the cover member 11 is in the second angularposition it is able to nest with the container member 9 by forwardmovement in the direction of arrow B. In other words, the concave cavity17 b of the shell-like cover member 11 is able to slidingly receive theconvex rear surface of the container member 9. In the nesting position,an interference fit is formed between the container and cover members 9,11 to releasable fasten them in the nesting position.

When the container and cover members 9,11 adopt the nestingconfiguration, an ergonomic unit is formed which is able to be easily,and comfortably, held by a hand 90 of a patient 92, as shown in FIG. 1.In this mode, the outer casing part 3 is able to act as a holder orapplicator of the drug delivery device 1.

As shown in FIG. 5, for example, the outer surface 33 at the rear sideof the container member 9 is provided with a window 35. As will beunderstood from FIGS. 4A and 4B, the window 35 is covered by the covermember 11 when in its second angular position. If the cover member 11 istransparent or semi-transparent, the window 35 is then visible throughthe cover member 11 when in its second angular position.

If need be, an indexing or detent mechanism could be provided forindexing the cover member 11 in one or more predetermined angularpositions about the pivot axis A-A, for instance the first and/or secondangular positions and/or angular positions therebetween. The user wouldthen have a tactile feedback indicating that the cover member 11 is inthe correct angular position, e.g. for nesting with the container member9. One way of achieving the indexing mechanism would be amale-and-female arrangement in which male (or female) surface featuresare formed in the outer surface 33 of the container member 9 at therequired angular dispositions about the pivot axis A-A and one or morecomplementary female (or male) surface features are correspondinglyarranged on the inner surface of the hinge 13 about the knob 15. Whenthe male feature is located in the, or one of the, female features (orvice-versa), the cover member 11 is indexed in a predetermined angularposition. To move the cover member 11 to a new angular position,rotation of the cover member 11 about the pivot axis A-A causesdisconnection of the first indexing connection until the male and femalefeatures re-engage at a new angular position of the cover member 11 Byway of example, a “ball-and-socket” indexing mechanism is shown in FIGS.8 and 9 in which a circular array of protrusions 80 is formed on theinner surface of the hinge 13 co-axially with the knob 15, and acomplementary circular array of sockets 82 is formed in the outersurface 33 of the bevel 29 on the container member 9 co-axially with thepivot axis A-A. When the protrusions 80 are located in the complementarysockets 82, the cover member 11 is indexed in one of a plurality ofdifferent predetermined angular positions it can adopt about the pivotaxis A-A, for instance the first angular position of FIGS. 2 and 3 orthe second angular position of FIGS. 4A and 4B. The cover member 11 isthen able to be indexed in a new predetermined angular position bypivoting it about the pivot axis A-A to disconnect and re-engage theprotrusions 80 and sockets 82, e.g. from the first angular position tothe second angular position and vice-versa.

In an alternative embodiment, an indexing mechanism may be providedwhich indexes the cover member 11 in an end angular position between thefirst and second angular positions mentioned previously such that thecover member 11 does not cover the window 35 in the container member 9,thereby allowing the window 35 to be viewed by a user of the intranasaldevice 1.

Canister Unit

Turning attention now to FIGS. 10A to 10D, the canister unit 7 comprisesan aerosol canister 10 of standard type which contains a drug formulatedin a fluid propellant, e.g. a liquefied gas propellant such as ahydrofluoro alkane (HFA), for instance 1,1,1,2-tetrafluoroethane(CF₃CH₂F) (known as “HFA 134a”) or 1,1,1,2,3,3,3-heptafluoro-n-propane(CF₃CHFCF₃) (known as “HFA 227”) or a mixture thereof. The drug istypically for the treatment or prophylaxis of respiratory diseases ordisorders, for example rhinitis. The drug may also be for the treatmentor prophylaxis of other types of disease or disorder through systemicaction of the drug. The canister unit 7 further comprises a dose counterhead 12.

The canister 10 has a metal canister body 14 which, as known in the art,e.g. from metered dose inhalers (MDIs), has an open end which is cappedby a valve assembly including a valve stem 16 which is mounted so it ismovable relative to the canister body 14, between a retracted or openposition relative to the canister body 14 in which the drug formulationis discharged from the canister 10 through the valve stem 16, and anextended or closed position relative to the canister body 14 in whichthe drug formulation is prevented from being discharged from thecanister 10.

As known in the art, the valve assembly includes a biasing mechanismsuch as a spring (not shown) for biasing the valve stem 16 to the closedposition. The valve assembly may be such as to further include ametering mechanism which operates so that a metered dose of the drugformulation is discharged when the valve stem 16 is in its openposition. Typically, the valve assembly will have a metering chamber offixed volume which in the closed position of the valve stem 16 is sealedfrom the external environment but in fluid communication with thecanister body 14 whereby the metering chamber is filled with the drugformulation, and which in the open position of the valve stem is sealedfrom the canister body 14 and its contents, but placed in fluidcommunication with the external environment so that the metered dose ofthe drug formulation in the chamber is discharged to the externalenvironment through the valve stem 16.

In this embodiment of the invention the valve assembly is a meteringvalve which dispenses a metered dose of the drug formulation peractuation thereof. A suitable metering valve is disclosed in WO98/29321,the content of which is hereby incorporated herein by reference.

The dose counter head 12 of the canister unit 7 has a hollow plasticsbody 18 of a plastics material which is fixedly secured to the canister10 over the outlet end of the canister 10 having the valve assembly. Thedose counter body 18 is fixed to the canister 10 to prevent it beingtaken off the canister 10, although it is free to rotate about alongitudinal axis D-D of the canister unit 7. The dose counter body 18may be fixed to the canister 10 in the manner described and shown inWO01/28887 (Glaxo/Brand et al), the content of which is herebyincorporated herein by reference.

As best shown in FIG. 10D, the dose counter body 18 is formed with adisplay window 20. The dose counter head 12 further includes a dosecounting mechanism (not shown) in the body 18 which, when actuated,advances a counter 22 thereof located in the window 20. When the counter22 is advanced it results in the dose count shown thereby in the window20 either being incremented to indicate the number of doses dispensedor, more preferably, decremented to show the number of doses left in thecanister 10. The dose counter mechanism can take one of the formsdescribed and shown in WO98/56444 (Glaxo/Rand et al) or Applicant'sco-pending International patent application No. PCT/EP03/06466(Applicant's Ref: PB60210), the contents of which are incorporatedherein by reference.

An aperture 24 is provided in the outer surface of the dose counter body18 to enable a driver to engage with the dose counting mechanism toadvance the counter 22 when a dose of the drug formulation is dispensedfrom the canister 10 by the inner actuating part 5, as will be describedin more detail hereinafter.

As shown in FIGS. 10A and 10B, the dose counter body 18 comprises askirt-like lower section 26 and a U-shaped upper section 28. The dosecounter body 18 also has a central opening 13 to the U-shaped uppersection 28 through which the valve stem 16 protrudes. It will further beseen from FIGS. 10C and 10D that the dose counter window 20 is formed ina protrusion 32 in the outer peripheral surface of the U-shaped uppersection 28.

Inner Actuating Part

Attention is now turned to FIGS. 11 to 15B which show the inneractuating part 5. The inner actuating part 5 is of a plastics material,preferably polypropylene, made by a moulding process, preferably byinjection moulding.

As will be seen, the inner actuating part 5 is of tubular constructionhaving a main body 37 defining an axially-oriented cavity 38. The mainbody 37 has an outer surface 39 having a rear section 40 of shape andsize which is complementary to the shape and size of the inner surface19 of the container member cavity 17 a, thereby enabling the inneractuating part 5 to fit snugly in the container member cavity 17 a, asshown in FIGS. 3 and 7, for example. More particularly, the rear section40 of the main body outer surface 39 is provided with a series ofaxially-spaced, circumferential ribs 41 a-c which act as spacers toposition the inner actuating part 5 along a vertical axis C-C in thecontainer member 9, as shown in FIGS. 6 and 7. Moreover, as furthershown in FIG. 7, the uppermost circumferential rib 41 a is adapted to besnap fit underneath the locking rib 21 a on the inner surface 19 of thecontainer member 9.

FIGS. 11 to 13 show that the circumferential ribs 41 a-c are intersectedby longitudinal slots 42, 44. The longitudinal slots 42, 44 arepositioned and sized so as to co-operate with the longitudinal ribs 27a, 27 b on the inner surface 19 of the container member 9 of the outercasing part 3 to prevent rotation of the inner actuating part 5 in thecontainer member 9 of the outer casing part 3.

It will further be seen that the inner actuating part 5 has a footstructure 43 which, as shown in FIG. 7, stands on a base surface 60 ofthe cavity 17 a of the container member 9. The foot structure 43includes a notch 45 on its forwardmost surface 47 which engages with thelocking rib 21 b at the lower end 25 of the cavity 17 a of the containermember 9. When the locking features 21 a, 21 b; 41 a, 45 of thecontainer member 9 and the inner actuating part 5 respectively engagewith one another, the inner actuating part 5 is releasably fixed inplace in the container member 9. Only when a sufficient separation forceis applied is the inner actuating part 5 released from the containermember 9.

The rear section 40 of the main body 37 of the inner actuating part 5has a longitudinally extending guide slot 49. The guide slot 49 is sizedto slidingly receive the protrusion 32 on the dose counter body 18. Thecanister unit 7 can only be inserted into the inner actuating part 5when the protrusion 32 is aligned with the guide slot 49 in the inneractuating part 5, as shown in FIG. 6. Thus, the guide slot 49 acts as atrack along which the protrusion 32 slidingly moves to insert thecanister unit 7 into the inner actuating part 5 and retract ittherefrom. The guide slot 49 also co-operates with the protrusion 32 toact as an anti-rotation feature which prevents rotation of the dosecounter head 12 in the inner actuating part 5, as will be understood byreference to FIGS. 12 and 13.

As shown in FIG. 13, the inner actuating part 5 also has longitudinalspacers 50 arranged circumferentially about the inner surface of thecavity 38 so that the canister unit 7 is generally co-axially mounted inthe inner actuating part 5.

At the base of the cavity 38 of the inner actuating part 5 there isprovided a hollow support 51 (so-called “stem block”) having a sleeve 52with a bore 53 sized to receive the valve stem 16 of the canister 10. Itwill be appreciated that when the canister unit 7 is inserted axiallyinto the cavity 38, the U-shaped upper section 28 of the dose counterhead 12 encloses the support 51 on three sides thereof. The hollowsupport 51 includes a hollow extension 55 which extends outwardly at anacute angle a to the outer periphery of the sleeve 52. The extension 55has a bore 57 which opens into the bore 53 of the sleeve 52.

The bore 57 of the extension 55 is co-axial with a longitudinal axis E-Eof a nozzle 59 which extends forwardly and upwardly at an acute angle βto the outer peripheral surface of the body 37 of the inner actuatingpart 5. The acute angles α, β may be the same, or substantially thesame. As shown in FIG. 1, the nozzle 59 is shaped and sized to bereceived in a nostril 94 of a nose 96 of the patient 92.

FIG. 15A shows the canister unit 7 mounted in the inner actuating part 5with the valve stem 16 held in the bore 53 of the sleeve 52 of thehollow support 51. As will be understood by comparing FIGS. 15A and 15B,in operation the canister body 14 (and counter head 12) is depressed inthe direction of arrow F relative to the inner actuating part 5 and thevalve stem 16, the stem 16 being held stationary in the hollow support51. This relative movement of the canister body 14 to the valve stem 16causes a metered dose of the drug formulation to be discharged throughthe valve stem 16 into the bore 53 of the sleeve 52. The drugformulation is then channeled by the extension 55 into the nozzle 59 fordelivery to the patient's nostril 94. The biasing mechanism in the valveassembly causes the canister body 14 to re-adopt the inoperativeposition shown in FIG. 15A on release of the depressing force F readyfor the next actuation cycle.

It can therefore be seen from the above that the inner actuating part 5contains all of the actuating elements for causing actuation of thecanister 10 so that the drug formulation is discharged therefrom intothe patient 92. In other words, the inner actuating part 5 is adapted toactuate the canister 10 when separate from the outer casing part 3.

Moreover, the base of the cavity 38 of the inner actuating part 5carries a rack-like post 61 having a serrated outer profile 63 (teeth)which co-operates with the dose counter mechanism such that ondepression of the canister body 14 in the inner actuating part 5 to itsoperative position shown in FIG. 15B, the rack-like post 61 drives a cogsystem in the dose counter mechanism (see WO98/56444 and PCT/EP03/06466supra) so that the counter 22 in the display 20 is advanced to reflectthat the canister 10 has been actuated to dispense a dose of the drugformulation.

It will be observed from FIGS. 11 to 13, for example, that the main body37 of the inner actuating part 5 has an aperture 100 through a sidethereof which is aligned with the rack-like post 61. The aperture 100 isleft by that member of the inner actuating part mould assembly used toform the post 61. In this regard, it will be gathered from FIG. 13 thatthe post 61 does not register with the nozzle 59. That is to say, thepost 61 is offset to the nozzle axis E-E such that it would not bepossible to have the mould member for the post 61 extracted through thenozzle 59. This is because the nozzle diameter has to be small enough tobe insertable into the patient's nostril 94 and the post 61 ispositioned to one side of the hollow support 51 which is in registrationwith the nozzle 59 for fluid communication therebetween.

As will be realised, the rack-like post 61 can be replaced by any otherdose counter mechanism driver structure as dictated by the form of thedose counter mechanism. Accordingly, the dose counter mechanism drivercan take the form of another type of mechanical element or anon-mechanical element, for example. Again, reference may be had toWO98/56444 supra.

It can be seen from FIG. 2 that once the canister unit 7 is assembledwith the inner actuating part 5 and this assembly snap-fitted into theouter casing part 3, the outer casing part 3 acts as a protective-casing for the canister unit 7 when in its closed state as it preventsactuation of the canister unit 7 and shields the nozzle 59 of the inneractuating part 5.

Operation

To use the intranasal device 1, the patient 92 moves the cover member 11of the outer casing part 3 from the closed position shown in FIG. 2 tothe open position shown in FIG. 3. The cover member 11 is then pivotedto the second angular position shown in FIG. 4A and then nested with thecontainer member 9, as shown in FIG. 4B. Then, as shown in FIG. 1, thepatient 92 grips the outer casing member 3 in one hand 90 and insertsthe nozzle 59 into the nostril 94. The patient 92 then actuates thedevice 1 by depressing the canister body 14 into the inner actuatingpart 5 relative to the valve stem 16 with the index finger 98. Thisresults in a metered dose of the drug formulation being delivered to thenostril.

Actuation of the device 1 can be confirmed by the patient 92 observingwhether the dose counter 22 has been advanced (decremented/incremented).The patient 92 then closes the outer casing part 3 to protect the inneractuating part 5 and canister unit 7 until the next dose is required tobe dispensed.

As will be seen from FIG. 1, when the outer casing part 3 is in its openstate it acts as a holder/applicator for the patient 92 in the sensethat the patient 92 is able to grip the outer casing part 3 in one hand90 and to depress the canister body 14 (and counter head 12) into theinner actuating part 5 with the index finger 98 to cause a dose of thedrug formulation to be dispensed through the nozzle 59 and the counter20 to be incremented/decremented.

One of the numerous advantages of the intranasal device 1 is the use ofseparable outer casing and inner actuating parts 3, 5. Recalling thatthe inner actuating part 5 contains all of the functional features foractuating the canister unit 7, both from a drug delivery and dosecounting point of view, this is the only part which needs to be testedand submitted for regulatory approval; The outer casing part 3 does notaffect the performance of the inner actuating part 5 in any way. Thiswould be in contrast to the case where the outer and inner parts 3, 5are integrally formed. In this instance, any change to the externalshape and configuration after approval would necessitate a newapplication for approval since the alteration may have an adverse effecton the internal functional features, especially if the component ismoulded from a plastics material.

So, the inner actuating part 5 is able to be designed first and then thedecorative outer protective casing part 3 designed afterwards. In thisway, the inner actuating part 5 can be tested and submitted forregulatory approval before the outer casing part 3 is finalised. Thisshortens the lead time for developing an approved drug delivery device.Moreover, the outer casing part 3 can be re-designed to maintain acontemporary appearance etc. without requiring a new round of regulatorytests.

Appropriate drugs (or medicaments) for use in the present invention, forinstance forming part of a pharmaceutical aerosol formulation having afluid propellant, e.g. a HFA propellant, such as HFA 134a or HFA 227,may be selected from, for example, analgesics, e.g., codeine,dihydromorphine, ergotamine, fentanyl or morphine; anginal preparations,e.g., diltiazem; antiallergics, e.g., cromoglycate (e.g. as the sodiumsalt), ketotifen or nedocromil (e.g. as the sodium salt); antiinfectivese.g., cephalosporins, penicillins, streptomycin, sulphonamides,tetracyclines and pentamidine; antihistamines, e.g., methapyrilene;anti-inflammatories, e.g., beclomethasone (e.g. as the dipropionateester), fluticasone (e.g. as the propionate ester), flunisolide,budesonide, rofleponide, mometasone (e.g. as the furoate ester),ciclesonide, triamcinolone (e.g. as the acetonide), 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carbothioicacid S-(2-oxo-tetrahydro-furan-3-yl) ester or 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioicacid S-fluoromethyl ester; antitussives, e.g., noscapine;bronchodilators, e.g., albuterol (e.g. as free base or sulphate),salmeterol (e.g. as xinafoate), ephedrine, adrenaline, fenoterol (e.g.as hydrobromide), formoterol (e.g. as fumarate), isoprenaline,metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol (e.g. asacetate), reproterol (e.g. as hydrochloride), rimiterol, terbutaline(e.g. as sulphate), isoetharine, tulobuterol or4-hydroxy-7-[2-[[2-[[3-(2-phenylethoxy)propyl]sulfonyl]ethyl]amino]ethyl-2(3H)-benzothiazolone;PDE4 inhibitors e.g. cilomilast or roflumilast; leukotriene antagonistse.g. montelukast, pranlukast and zafirlukast; [adenosine 2a agonists,e.g.2R,3R,4S,5R)-2-[6-Amino-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-5-(2-ethyl-2H-tetrazol-5-yl)-tetrahydro-furan-3,4-diol(e.g. as maleate)]; [α4 integrin inhibitors e.g.(2S)-3-[4-({[4-(aminocarbonyl)-1-piperidinyl]carbonyl}oxy)phenyl]-2-[((2S)-4-methyl-2-{[2-(2-methylphenoxy)acetyl]amino}pentanoyl)amino]propanoic acid (e.g. as free acid or potassium salt)], diuretics, e.g.,amiloride; anticholinergics, e.g., ipratropium (e.g. as bromide),tiotropium, atropine or oxitropium; hormones, e.g., cortisone,hydrocortisone or prednisolone; xanthines, e.g., aminophylline, cholinetheophyllinate, lysine theophyllinate or theophylline; therapeuticproteins and peptides, e.g., insulin or glucagons. It will be clear to aperson skilled in the art that, where appropriate, the medicaments maybe used in the form of salts, (e.g., as alkali metal or amine salts oras acid addition salts) or as esters (e.g., lower alkyl esters) or assolvates (e.g., hydrates) to optimise the activity and/or stability ofthe medicament and/or to minimise the solubility of the medicament inthe propellant.

Preferably, the medicament is for the treatment of inflammatory and/orallergic conditions of the nasal passages such as rhinitis, e.g.seasonal and perennial rhinitis as well as other local inflammatoryconditions such as asthma, COPD and dermatitis. Preferably, themedicament is an anti-inflammatory compound for the treatment of asthmaor rhinitis.

It is to be understood that the exemplary embodiments of the presentinvention outlined above are for the purposes of illustration only, andthat the invention can be modified, varied and take on other guiseswithin the scope of the appended claims. Mindful of this, the use ofreference numerals in the claims is not to be taken as having a limitingeffect on the scope of the claims.

For the avoidance of doubt, the use herein of terms such as “generally”,“substantially”, “about” and the like when referring to a parameter ofthe invention is meant to include the absolute parameter.

1. A drug delivery device for delivering to a patient a drug compositionfrom a container which contains the drug composition, the containeradapted to be placed in a dispensing mode thereof on application of anactuating condition thereto, wherein the device comprises: a dispensingunit adapted to receive the container, the dispensing unit having anactuating mechanism operable to apply the actuating condition to thecontainer and an outlet through which the drug composition isdispensable from the device; and a removable casing unit for thedispensing unit; and wherein: the dispensing and casing units havesecuring features for releasably, fixedly securing the units together;and the dispensing unit is operable to apply the actuating condition tothe container when fixedly secured to the casing unit and whenindependent from the casing unit.
 2. The device of claim 1, wherein thecasing unit is movable between a closed state in which it is able toenclose the dispensing unit with the container received therein, and anopen state which enables the actuating mechanism of the dispensing unitto be operated to apply the actuating condition to the container and forthe resultant dispensed drug composition to be discharged from theoutlet.
 3. The device of claim 1 which is hand-held.
 4. The device ofclaim 3 in which the device is adapted to be held by the casing unitwhen assembled with the dispensing unit.
 5. The device of claim 1 inwhich the dispensing unit is adapted to be hand-operated to apply theactuating condition to the container.
 6. The device of claim 5 adaptedso that, when the casing unit is held by a hand of a patient, the handof the patient is also able to operate the actuating mechanism of thedispensing unit.
 7. The device of claim 1 wherein the actuatingcondition is movement of a first part of the container relative to asecond part and the actuating mechanism of the dispensing unit is ableto effect said relative movement.
 8. The device of claim 7 wherein theactuating mechanism of the dispensing unit is adapted in use to hold thesecond part of the container stationary and to allow the first part tomove relative thereto.
 9. The device of claim 1 wherein the containerhas a plurality of doses of the drug composition and is fitted with adose counter mechanism, and wherein the dispensing unit has a dosecounter advancing mechanism adapted in use to advance the dose countermechanism when the actuating condition is applied by the dispensing unitto the container.
 10. The device of claim 9 wherein the actuatingcondition is movement of a first part of the container relative to asecond part and the actuating mechanism of the dispensing unit is ableto effect said relative movement and in which the dose counter advancingmechanism has a mechanical feature which engages the dose countermechanism to advance it on relative movement of the first part of thecontainer to the second part thereof.
 11. The device of claim 10 inwhich the mechanical feature is a post.
 12. The device of claim 10 inwhich the mechanical feature is a part of a rack-and-pinion mechanism,the other part being in the dose counter mechanism.
 13. The device ofclaim 1 in which the outlet forms a part of a nozzle arrangement in thedispensing unit for directing the drug composition to the patient onapplication of the actuating condition to the container.
 14. The deviceof claim 7, wherein the second part of the container presents an outletof the container.
 15. The device of claim 13 wherein, the outlet of thecontainer is held stationary by the nozzle arrangement.
 16. The deviceof claim 7, wherein the second part is a valve which is moved between aclosed position and an open position on relative movement with the firstpart.
 17. The device of claim 16, wherein the container is an aerosolcontainer with the first part a canister.
 18. The device of claim 1further comprising the container and the drug composition therein. 19.The device of claim 18 in which the drug composition is for thetreatment or prophylaxis of a respiratory disease or disorder.
 20. Thedevice of claim 1 which is an inhalation device or an intranasal device.21. A drug delivery system comprising the device of claim 1 and at leastone further dispensing unit, the dispensing units being interchangeablewith one another.
 22. A method of manufacturing a drug delivery devicefor delivery of a drug formulated in a drug container which is adaptedto be placed in a dispensing mode on application of an actuatingcondition thereto, the method comprising the steps of: providing adispensing unit for receiving the container which has an actuatingmechanism for applying the actuating condition thereto and an outletthrough which the drug formulation is dispensed on application of theactuating condition to the container, and separately providing a casingunit adapted to fixedly hold the dispensing unit such that the drug isdispensable from the container by the dispensing unit when held by thecasing unit.
 23. The method of claim 23 in which the casing unit has aclosed state in which it forms a protective casing around the dispensingunit and an open state in which it provides access to the dispensingunit.
 24. The method of claim 22 in which the drug delivery device ishand-held and hand-operable.
 25. The method of claim 22 in which thedispensing unit is provided with at least a part of a dose countingmechanism.
 26. The method of claim 22 in which the drug container has adose counter and the dispensing unit has a dose counter advancingmechanism for advancing the dose counter on application of the actuatingcondition.
 27. The method of claim 26 in which the dose counteradvancing mechanism is a mechanical mechanism.
 28. The method of claim27 in which the dose counter advancing mechanism is a mechanical memberin the casing unit which interengages with the dose counter to advanceit on application of the actuating condition.
 29. The method of claim 28in which the mechanical member is a rack-like member.
 30. The method ofclaim 22 in which the dispensing unit provides for relative movement ofthe container therewith and the actuating mechanism is such as to applythe actuating condition on such relative movement.
 31. The method ofclaim 30 in which the dispensing unit has a valve stem support forreceiving a valve stem of a valve mechanism of the container, relativemovement of the container to the dispensing unit causing depression ofthe valve stem for release of a dose of the drug from the container. 32.The method of claim 22 in which the outlet of the dispensing unit is anexhaust duct for channeling the drug to the external environment whenreleased from the container.
 33. A drug delivery device formed by themethod of claim
 22. 34-35. (canceled)